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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Resistance to oxyimino-cephalosporins conferred by an alternative mechanism of hydrolysis by the Acinetobacter -derived cephalosporinase-33 (ADC-33), a class C β-lactamase present in carbapenem-resistant Acinetobacter baumannii (CR Ab )

ABSTRACT Antimicrobial resistance inAcinetobacter baumanniiis partly mediated by chromosomal class C β-lactamases, theAcinetobacter-derived cephalosporinases (ADCs). Recently, a growing number of emerging variants were described, expanding this threat. Consistent with other β-lactamases, one of the main areas of variance exists in the Ω-loop region near the site of cephalosporin binding. Interestingly, a common alanine duplication (Adup) is found in this region. Herein, we studied specific Adup variants expressed in a uniformEscherichia coligenetic background that demonstrated high-level resistance to multiple oxyimino-cephalosporins. For ceftolozane and ceftazidime, the Adup ADCs significantly increased levels of resistance (minimum inhibitory concentration [MIC] ≥ 512 µg/mL and MIC ≥ 1,024 µg/mL, respectively). These observations were consistent with the increasedk cat /K M for ceftazidime. For cefiderocol, three Adup variants exhibited increased MICs and increasedk cat /K M for this compound. Timed electrospray ionization mass spectrometry demonstrated stable cephalosporin:ADC adducts with ADC-30 (non-Adup), but not with ADC-33 (Adup), consistent with turnover. The X-ray crystal structure of Adup variant ADC-33 in complex with ceftazidime was determined (1.57 Å resolution) and suggests that increased turnover is facilitated by conformational changes (shift in Tyr221 and orientation of the oxyimino portion of the R1 side chain) and repositioning of water in the active site. These changes appear to favor substrate-assisted catalysis as an alternative mechanism to base-assisted catalysis. These studies also provide unprecedented insight into the mechanism underlying oxyimino-cephalosporin hydrolysis by expanded-spectrum ADC β-lactamases and possibly other class C β-lactamases, which is of critical importance to future drug design. IMPORTANCE The characterization of emergingAcinetobacter-derived cephalosporinase (ADC) variants is necessary to understand the increasing resistance to β-lactam antibiotics inAcinetobacterspp. In this study, cefiderocol retains effectiveness against ADC variants with and without an Ω-loop alanine duplication (Adup). However, the presence of the Adup appears to introduce loop flexibility and structural alterations resulting in increased resistance and steady-state turnover of larger cephalosporins. Further characterization provides unprecedented insight into the mechanism of cephalosporin hydrolysis by ADC β-lactamases and supports a concomitant increase in ADC structural flexibility and cephalosporin affinity that leads to more efficient hydrolysis. In addition, the crystal structure of ADC-33 in complex with ceftazidime is consistent with a substrate-assisted catalysis mechanism. The structural differences in the ADC-33 active site leading to ceftazidime catalysis provide a better understanding of β-lactamase Adup variants and open important opportunities for future drug design and development.

Microbiology↗
DOE OSTI2023

BeyondPlanck: V. Minimal ADC Corrections for Planck LFI

We describe the correction procedure for Analog-to-Digital Converter (ADC) differential non-linearities (DNL) adopted in the Bayesian end-to-end BEYONDPLANCK analysis framework. This method is nearly identical to that developed for the official Planck Low Frequency Instrument (LFI) Data Processing Center (DPC) analysis, and relies on the binned rms noise profile of each detector data stream. However, rather than building the correction profile directly from the raw rms profile, we first fit a Gaussian to each significant ADC-induced rms decrement, and then derive the corresponding correction model from this smooth model. The main advantage of this approach is that only samples which are significantly affected by ADC DNLs are corrected, as opposed to the DPC approach in which the correction is applied to all samples, filtering out signals not associated with ADC DNLs. The new corrections are only applied to data for which there is a clear detection of the non-linearities, and for which they perform at least comparably with the DPC corrections. Out of a total of 88 LFI data streams (sky and reference load for each of the 44 detectors) we apply the new minimal ADC corrections in 25 cases, and maintain the DPC corrections in 8 cases. All these corrections are applied to 44 or 70 GHz channels, while, as in previous analyses, none of the 30 GHz ADCs show significant evidence of non-linearity. By comparing the BEYONDPLANCK and DPC ADC correction methods, we estimate that the residual ADC uncertainty is about two orders of magnitude below the total noise of both the 44 and 70 GHz channels, and their impact on current cosmological parameter estimation is small. However, we also show that non-idealities in the ADC corrections can generate sharp stripes in the final frequency maps, and these could be important for future joint analyses with the Planck High Frequency Instrument (HFI), Wilkinson Microwave Anisotropy Probe (WMAP), or other datasets. We therefore conclude that, although the existing corrections are adequate for LFI-based cosmological parameter analysis, further work on LFI ADC corrections is still warranted.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

A Radiation-Hard 8-Channel 15-Bit 40-MSPS ADC for the ATLAS Liquid Argon Calorimeter Readout

The custom design of a radiation-hardened, 8-channel, 40-MSPS, 15-bit resolution, 14.2-bit dynamic range, 11.4-ENOB ADC data acquisition ASIC fabricated in a commercial 65-nm triple-well CMOS technology is presented. The ADC is developed for and integrates seamlessly into the readout system for the ATLAS liquid argon (LAr) calorimeter in the high-luminosity large hadron collider (HLLHC) upgrade at CERN, which will require a total of 364 936 ADC channels. A three-stage MDAC+SAR pipelined ADC architecture was designed to meet the physics requirements and scientific goals of the ATLAS experiment. The ADC is a fully self-contained data acquisition system that includes foreground calibration, digital data processing, digital control, and supporting circuitry. The measured performance shows the ADC achieves a competitive dynamic range and SNDR, and it meets or exceeds the ATLAS analog requirements. Radiation tolerance and scalability design considerations were implemented at the device-, circuit-, and system-level. Radiation-hardening-by-design techniques used include redundancy for digital circuits, the use of MiM capacitors, and a hybrid RC-DAC for the ADC core. The ADC ASIC was demonstrated to be robust against the effects of the intense radiation expected in the HL-LHC experimental environment.

DAQ↗
DOE OSTI2021

Compact, low power, high resolution ADC per pixel for large area pixel detectors

A compact ADC circuit can include one or more comparators, and a serial DAC (Digital-to-Analog) circuit that provides a signal to the comparator (or comparators). In addition, the ADC circuit can include a serial DAC redistribution sequencer that can provide a plurality of signals as input to the serial DAC circuit and is subject to a redistribution cycle and which receives as input a signal from a data multiplexer whose input connects electronically to an output of the comparator. The circuit can further include an ADC code register that provides an ADC output that connects electronically to the output of the comparator and the input to the data multiplexer. Shared logic circuitry for sharing common logic between pixels can be included, wherein the shared logic circuitry connects electronically to the data multiplexer and the ADC code register, wherein the shared logic circuitry promotes area and power savings for the pixel detector circuit.

Zimmerman, Tom↗
DOE OSTI2023

Compact, low power, high resolution ADC per pixel for large area pixel detectors

A compact ADC circuit can include one or more comparators, and a serial DAC (Digital-to-Analog) circuit that provides a signal to the comparator (or comparators). In addition, the ADC circuit can include a serial DAC redistribution sequencer that can provide a plurality of signals as input to the serial DAC circuit and is subject to a redistribution cycle and which receives as input a signal from a data multiplexer whose input connects electronically to an output of the comparator. The circuit can further include an ADC code register that provides an ADC output that connects electronically to the output of the comparator and the input to the data multiplexer. Shared logic circuitry for sharing common logic between pixels can be included, wherein the shared logic circuitry connects electronically to the data multiplexer and the ADC code register, wherein the shared logic circuitry promotes area and power savings for the pixel detector circuit.

Fahim, Farah↗
DOE OSTI2025

Evolution of carbapenemase activity in the class C β-lactamase ADC-1

Antibiotic resistance in bacteria poses a significant threat to public health. Among dozens of available antimicrobial agents, carbapenems are used as drugs of choice for the treatment of serious infections caused by pathogens resistant to other antibiotics. However, their usefulness has been severely compromised due to the emergence and wide spread of carbapenem-resistant clinical isolates worldwide. High-level resistance to carbapenems in bacteria is mediated by the production of β-lactamases from three molecular classes, A, B, and D, but not by class C enzymes. In this study, we selected a triple mutant of the intrinsic class C Acinetobacter-derived cephalosporinase ADC-1 (ADC-1 TM ) that confers high-level resistance to the carbapenems meropenem, ertapenem, and doripenem. Kinetic experiments demonstrated that the apparent binding affinity, along with the acylation and deacylation rates, were all improved for the mutant enzyme. X-ray crystallography, molecular docking, and molecular dynamics simulations revealed that the amino acid substitutions in ADC-1 TM produce significant changes in the enzyme active site architecture and binding mode of the carbapenem ertapenem. These changes allow for better positioning of a deacylating water for nucleophilic attack, thus explaining the significantly improved rate of ertapenem deacylation by ADC-1 TM . In this study, we showed for the first time that a class C β-lactamase can produce high-level resistance to carbapenem antibiotics, which underlines the potential for enzymes of this class to evolve such resistance and could further exacerbate the problem of antibiotic resistance in bacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Sulfonamidoboronic Acids as “Cross-Class” Inhibitors of an Expanded-Spectrum Class C Cephalosporinase, ADC-33, and a Class D Carbapenemase, OXA-24/40: Strategic Compound Design to Combat Resistance in Acinetobacter baumannii

Acinetobacter baumannii is a Gram-negative organism listed as an urgent threat pathogen by the World Health Organization (WHO). Carbapenem-resistant A. baumannii (CRAB), especially, present therapeutic challenges due to complex mechanisms of resistance to β-lactams. One of the most important mechanisms is the production of β-lactamase enzymes capable of hydrolyzing β-lactam antibiotics. Co-expression of multiple classes of β-lactamases is present in CRAB; therefore, the design and synthesis of “cross-class” inhibitors is an important strategy to preserve the efficacy of currently available antibiotics. To identify new, nonclassical β-lactamase inhibitors, we previously identified a sulfonamidomethaneboronic acid CR167 active against Acinetobacter-derived class C β-lactamases (ADC-7). The compound demonstrated affinity for ADC-7 with a K i = 160 nM and proved to be able to decrease MIC values of ceftazidime and cefotaxime in different bacterial strains. Herein, we describe the activity of CR167 against other β-lactamases in A. baumannii: the cefepime-hydrolysing class C extended-spectrum β-lactamase (ESAC) ADC-33 and the carbapenem-hydrolyzing OXA-24/40 (class D). These investigations demonstrate CR167 as a valuable cross-class (C and D) inhibitor, and the paper describes our attempts to further improve its activity. Five chiral analogues of CR167 were rationally designed and synthesized. The structures of OXA-24/40 and ADC-33 in complex with CR167 and select chiral analogues were obtained. The structure activity relationships (SARs) are highlighted, offering insights into the main determinants for cross-class C/D inhibitors and impetus for novel drug design.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Structural Characterization of Linker Shielding in ADC Site-Specific Conjugates

Background/Objectives: Antibody–Drug Conjugates (ADCs) have rapidly evolved from early, rudimentary conjugates to highly targeted and precisely engineered molecules. Despite notable clinical successes, ADCs continue to face significant challenges, including aggregation and high hydrophobicity driven by high drug-to-antibody ratios (DARs), premature payload release, dose-limiting toxicities, and suboptimal pharmacokinetics. While site-specific linker–payload conjugation has improved ADC homogeneity and stability, the structural basis of antibody–linker interactions at specific sites remains underexplored. Methods: In this work, we present the crystal structures of trastuzumab Fab and Fc domains site-specifically conjugated with a cleavable linker–payload. Results: Our findings suggest that pockets within both Fab and Fc regions may interact with and shield the linker portion of the conjugate. Conclusions: These insights highlight the previously underappreciated potential of structure-based design to drive the optimization of ADC linker chemistry and facilitate the co-design of bespoke linker–payloads tailored to individual antibody conjugation sites.

Jaime-Garza, Maru [Discovery Chemistry, Merck & Co↗
DOE OSTI2024

A Cryogenic readout integrated circuit with analog pile-up and in-Pixel ADC for high frame rate Skipper CCD-in-CMOS Sensors

The Skipper CCD-in-CMOS Parallel Read-Out Circuit V2 (SPROCKET2) is designed to enable high frame rate readout of Skipper CCD-in-CMOS image sensors. The SPROCKET2 pixel is fabricated in a 65 nm CMOS process and occupies a 60$\mu$m $\times$ 60$\mu$m footprint. SPROCKET2 is intended to be heterogeneously integrated with a pixelated Skipper CCD-in-CMOS sensor, such that one readout pixel is connected to a multiplexed array of 16 active image sensor pixels, to match their spatial geometry. Our design benefits from the Skipper CCD-in-CMOS sensor's non-destructive readout capability to achieve exceptionally low noise through multi-sampling and averaging while optimizing for total power consumption. The pixel readout utilizes correlated double sampling to minimize 1/f noise and includes "pile-up" of ten successive samples in the analog domain before digitizing at a rate of 66.7 ksps. Measurement results of in-pixel serial SAR ADC show DNL and INL of ~0. 44 LSB and 0.58 LBS respectively. A large area array of 20,000 SPROCKET2 ADC pixels (multiplexed 1:16 to 320,000 sensor pixels) is currently under test. By reading out data over a 10 Gbps optical link, this pixel design enables a frame rate of $\sim$ 4 kfps for large sensing areas with minimal sensing deadtime. In the highest gain mode, the pixelated ADC has an input-referred resolution of 10$\mu$V with a simulated power consumption of 50$\mu$W. The pixel operates with constant current draw to minimize power-rail crosstalk.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2020

A pixel detector ROIC with a 3-bit, 40 Msps synchronous ADC per pixel for HL LHC

The prototype Fermi Compact Muon Solenoid (CMS) Pixel (FCP130), manufactured in a 130 nm process, is a readout integrated circuit (ROIC) designed for the High Luminosity upgrade of the Large Hadron Collider. It employs a synchronous analog to digital converter (ADC) for the front-end design, with signal processing and data conversion within a single bunch crossing of 25 ns. It is therefore capable of accurately detecting hits occurring in consecutive bunch crossings, without off-time registration of events, making it particularly suitable for the inner most layers of the vertex detector. The ROIC consists of a matrix of 48 × 160 pixels, each 100 × 30 μm2 in size. Each pixel contains a charge sensitive preamplifier with self-biasing leakage current compensation, eight auto-zero comparators and a Gray code encoder for a 3-bit flash-type ADC. The total power consumption is approximately 24 μW per pixel. The measured noise at the output of all the hit comparators across the ROIC is < 80 e- with threshold dispersion < 110 e-RMS, which allows an in-time threshold setting of ~ 1000 e-.

43 PARTICLE ACCELERATORS↗
DOE OSTI2023

In-Pixel Readout IC with compact in-pixel ADC for Pixel detectors at HL LHC

The prototype Smart Pixel concept test chip (SP28), designed in a CMOS 28 nm bulk process, is a proof of concept readout integrated circuit (ROIC) designed for a future Phase III High Luminosity upgrade of the Large Hadron Collider. It employs a synchronous analog to digital converter (ADC) for the front-end design, with signal processing and data conversion within a single bunch crossing of 25 ns. It is therefore capable of accurately detecting hits occurring in consecutive bunch crossings, without off-time registration of events and pileup insensitivity, making it particularly suitable for the inner most layers of the vertex detector. The ROIC consists of a matrix of 32 × 16 pixels, each 25 × 25 µm 2 in size. Each pixel contains a charge sensitive preamplifer with leakage current compensation, three auto-zero comparators for a 2-bit fash-type ADC. The total power consumption is approximately 5 µW per pixel. The measured noise at the output of all the hit comparators across the ROIC is < 90 e- with threshold dispersion < 45 e-RMS, which allows an in-time threshold setting of ≈ 475 e-.

Parpillon, Benjamin↗
DOE OSTI2023

A Cryogenic Readout IC with 100 KSPS in-Pixel ADC for Skipper CCD-in-CMOS Sensors

The Skipper CCD-in-CMOS Parallel Read-Out Circuit (SPROCKET) is a mixed-signal front-end design for the readout of Skipper CCD-in-CMOS image sensors. SPROCKET is fabricated in a 65 nm CMOS process and each pixel occupies a 50$\mu$m $\times$ 50$\mu$m footprint. SPROCKET is intended to be heterogeneously integrated with a Skipper-in-CMOS sensor array, such that one readout pixel is connected to a multiplexed array of nine Skipper-in-CMOS pixels to enable massively parallel readout. The front-end includes a variable gain preamplifier, a correlated double sampling circuit, and a 10-bit serial successive approximation register (SAR) ADC. The circuit achieves a sample rate of 100 ksps with 0.48 $\mathrm{e^-_{rms}}$ equivalent noise at the input to the ADC. SPROCKET achieves a maximum dynamic range of 9,000 $e^-$ at the lowest gain setting (or 900 $e^-$ at the lowest noise setting). The circuit operates at 100 Kelvin with a power consumption of 40 $\mu W$ per pixel. A SPROCKET test chip was submitted in September 2022, and test results will be presented at the conference.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2023

The COLUTA ADC ASIC and the ATLAS HL-LHC Liquid Argon Front-End Readout

Abstract The upgraded High-Luminosity Large Hadron Collider (HL-LHC) requires a new radiation tolerant ATLAS Liquid Argon (LAr) Calorimeter readout operating at 40 MHz with 16-bit dynamic range. The Front-End Board 2 (FEB2) will provide the front-end readout for the calorimeter, and will interface a series of custom ASICs due to radiation tolerance requirements of the HL-LHC. The COLUTA is a 65 nm CMOS custom 8-channel 15-bit 40 MSPS ADC ASIC developed for this application. This contribution will present performance results of the final prototype of the COLUTA, surpassing specifications at >11.5 ENOB for relevant frequencies, as well as non-linearity and radiation requirements. Preliminary integration results of the front-end readout components will also be described by means of the FEB2 Pre-Prototype, the “Slice Testboard”.

Instruments & Instrumentation↗
DOE OSTI2025

Muon tagging with flash ADC waveform baselines

Here, this manuscript describes an innovative method to tag muons using the baseline information of the Flash ADC (FADC) waveform of PMTs in the JSNS 2 (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) experiment. The experiment is designed to search for evidence of sterile neutrinos, and a reliable method for muon tagging is an essential component for background rejection because the detector is located above ground, on the 3rd floor of the J-PARC Material and Life Science Experimental Facility (MLF). Cosmogenic muons that stop within the detector volume and produce a Michel electron are a particularly important background that must be rejected for our sterile neutrino search. Utilizing this innovative method, more than 99.8 % of Michel electrons can be rejected even without using information from the detector’s veto region PMTs. This technique can be employed by any experiments which uses a similar detector configuration.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2020

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the MAJORANA DEMONSTRATOR 76 Ge neutrinoless double beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearites. Here, a simple measurement protocol was developed that did not require sophisticated equipment or lengthy data taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearites by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2023

Chip Development Toward 12 bit 10 GSPS Cryogenic ADC for Multiplexed Quantum Readout

This presentation presents the background and plan for the development toward a 12 bit 10 GSPS cryogenic ADC for multiplexed quantum readout. It covers the first two chips that have been taped out and tested. It includes results for those chips and provides some context to plans for the upcoming chip tapeout and the final one to come later.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2023

Physical Layer Security at a Point-to-Point MIMO System With 1-Bit DACs and ADCs

Low-resolution converters reduce the power consumption of wireless devices and help enable large energy-efficient arrays. In this letter, we evaluate the secrecy rate for the extreme case of 1-bit single-user multiple-input multiple-output systems following two signaling approaches. In the first method, the system uses discrete signaling. In the second, the system combines Gaussian signaling with artificial noise alongside power allocation. In the first case, we give a closed-form expression of the secrecy rate and propose an algorithm that provides near-optimal results for low signal-to-noise ratios (SNRs). Further, in the second scenario, depending on the channel state information, we suggest different precoding plans and derive a secrecy rate lower bound. At low SNR, power is allocated to the main signal. Only at high SNR is optimal power allocation effective. Moreover, knowing the eavesdropper channel greatly improves the system’s secrecy.

1-bit digital-to-analog (DAC) and analog-to-digita↗